A dose-escalation regimen of trimethoprim–sulfamethoxazole is tolerable for prophylaxis against Pneumocystis jiroveci pneumonia in rheumatic diseases

Takenaka, Kenchi; Komiya, Yoji; M, Ota; Yamazaki, Haruka; Nagasaka, Kenji

doi:10.3109/s10165-012-0730-x

Cited by 13 publications

(7 citation statements)

References 29 publications

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“…The incidence rates of AEs that required discontinuation of SMX/TMP were lower in HS (8.5%) and ES (9.1%) compared to SS (20.7%), although there was no statistically significant difference. These figures were consistent with the previously reported SMX/TMP discontinuation rates of 8.5–17.9% in patients with rheumatic diseases [33, 37]. AEs that required a reduction in the dose of SMX/TMP were significantly more frequent in SS compared to the other groups.…”

Section: Discussionsupporting

confidence: 92%

“…The primary objective of this study was to show non-inferiority of ES to SS in terms of non-incidence rates of PJP at week 24. No patients developed PJP by week 24; thus, we estimated the non-incidence rates of PJP using the exact confidence interval [33] as a post-hoc analysis. The secondary objectives were to compare PJP non-incidence rates between HS and SS, and drug retention rates and safety among the three groups.…”

Section: Methodsmentioning

confidence: 99%

“…With respect to sample size, we assumed the PJP non-incidence rate in SS to be 93% and that in ES to be 98%, assuming that a lower discontinuation rate in the latter would result in better efficacy [23, 33]. We set a non-inferiority limit of 5%, one-sided α of 0.05, and β of 0.20.…”

Section: Methodsmentioning

confidence: 99%

“…Takenaka et al [33] conducted a retrospective study to compare the effectiveness and safety of the conventional regimen (one daily single-strength tablet of SMX/TMP, 400 mg/80 mg) and the dose escalation regimen (started with the 10% dose of one single-strength tablet and increased the dose by 10% per week). They reported that there was no significant difference in the prophylactic effect on PJP; however, the drug retention rate of the dose escalation regimen group was better than that of the conventional regimen group.…”

Section: Introductionmentioning

confidence: 99%

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Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial

et al. 2017

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BackgroundSulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis pneumonia (PJP) in immunosuppressed patients with systemic rheumatic diseases, but is sometimes discontinued due to adverse events (AEs). The objective of this non-blinded, randomized, 52-week non-inferiority trial was to quest an effective chemoprophylaxis regimen for PJP with a low drug discontinuation rate. Results at week 24 were reported.MethodsAdult patients with systemic rheumatic diseases who started prednisolone ≥0.6 mg/kg/day were randomized into three dosage groups: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group (HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, increasing incrementally to 200/40 mg daily). The primary endpoint was non-incidence rates (non-IR) of PJP at week 24.ResultsOf 183 patients randomly allocated at a 1:1:1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES started SMX/TMP. A total of 172 patients were included in the analysis. No cases of PJP were reported up to week 24. Estimated non-IR of PJP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was 96.8–100% using the exact confidence interval as a post-hoc analysis. The overall discontinuation rate was significantly lower with HS compared to SS (p = 0.007). The discontinuation rates due to AEs were significantly lower with HS (p = 0.006) and ES (p = 0.004) compared to SS. The IR of AEs requiring reduction in the dose of SMX/TMP (p = 0.009) and AEs of special interest (p = 0.003) were different among the three groups with significantly higher IR in SS compared to HS and ES.ConclusionsAlthough there were no PJP cases, the combined group of HS and ES had an excellent estimated non-IR of PJP and both were superior in safety to SS. From the perspective of feasibility and drug discontinuation rates, the daily half-strength regimen was suggested to be optimal for prophylaxis of PJP in patients with systemic rheumatic diseases.Trial registrationThe University Hospital Medical Information Network Clinical Trials Registry number is UMIN000007727, registered 10 April 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1206-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial

et al. 2017

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“…Takenaka et al [21] conducted a retrospective study to compare the conventional regimen and the dose escalation regimen. The dose escalation regimen is initiated with a 10% dose of one single-strength tablet; the dose is increased by 10% per week.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of reduced-dose sulfamethoxazole-trimethoprim for chemoprophylaxis ofPneumocystispneumonia in patients with rheumatic diseases

Harada

Kato

Sueda

et al. 2020

Modern Rheumatology

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Is cotrimoxazole prophylaxis against Pneumocystis jirovecii pneumonia needed in patients with systemic autoimmune rheumatic diseases requiring immunosuppressive therapies?

et al. 2021

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A dose-escalation regimen of trimethoprim–sulfamethoxazole is tolerable for prophylaxis against Pneumocystis jiroveci pneumonia in rheumatic diseases

Abstract: In rheumatic diseases, a dose-escalation regimen of TMP/SMX resulted in a higher retention rate and was safer than the routine regimen.

Cited by 13 publications

References 29 publications

Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial

Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial

The efficacy and safety of reduced-dose sulfamethoxazole-trimethoprim for chemoprophylaxis ofPneumocystispneumonia in patients with rheumatic diseases

Is cotrimoxazole prophylaxis against Pneumocystis jirovecii pneumonia needed in patients with systemic autoimmune rheumatic diseases requiring immunosuppressive therapies?

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